Differentiation among malignant lymphomas and leukemias affects how aggressively patients are treated, which medications are appropriate, and what levels of risk are justified. As more differentiated treatments become available, it has become increasingly important to distinguish among subclasses of blood pathologies. Nonetheless, discriminating among known pathologies may be difficult. As an example, mantle cell lymphoma (“MCL”) is often misdiagnosed as chronic lymphocytic leukemia (“CLL”) or as follicular center cell lymphoma (“FCC”).
The classical morphological description of MCL is a monotonous proliferation of small to medium sized lymphoid cells with scant cytoplasm, variably irregular and indented nuclei, dispersed chromatin, inconspicuous nucleoli and scant cytoplasm. The immunophenotype is CD5 positive B cells which are FMC7 antigen positive with moderately bright surface membrane immunoglobin light chain expression, CD2d negative and usually CD10 negative. The lack of CD23 expression differentiates this entity from typical CLL, however confusion between these two can arise when CLL loses CD23 during disease progression.
The classical morphological description of typical CLL cells is small lymphocytes containing round nuclei with coarsely condensed chromatin and scant cytoplasm. The immunophenotype for CLL is CD5 positive antigen expression on B cells with CD23 antigen positivity, low density surface membrane immunoglobulin restricted light chain positivity and CD10 negative. This immunophenotype is considered the diagnostic gold standard for CLL. However, atypical CLL may be associated with deviations in immunophenotype that lead to a misdiagnosis as mantle cell lymphoma.
The classical morphological description of FCC cells is small to medium sized lymphoid cells with markedly angulated and cleaved nuclei, coarse chromatin, inconspicuous nucleoli and scant cytoplasm. The classic immunophenotype consists of CD5 negative B cells with positive CD10 expression and moderately bright expression of surface membrane immunoglobulin light chain expression.
The subtle visual differences exhibited by these pathologies give rise to a significant number of false negatives during routine screening. When suspicious cells are detected, subsequent evaluation of specimens by even experienced pathologists may be inconclusive. In these cases a diagnosis is not rendered until the specimen has been immunophenotyped. Additional testing is expensive, time-consuming, and often requires fresh tissue which may not be readily available. Because it would be impractical to immunophenotype every specimen, it would be useful to reduce the frequency of false negatives and improve discrimination among commonly confused lymphoproliferative disorders without resort to immunophenotyping. The timely diagnosis of, for example, MCL is of extreme importance since it has a more aggressive clinical course.
There remains a need for diagnostic tools to assist in discriminating among pathologies with similar characteristics and different courses of treatment.